Diet-induced obesity is associated with worse stroke outcome and increased susceptibility to post storke infection

Objectives: Obesity, with increasing prevalence in western societies, positively correlates with an increased risk for ischemic stroke. We have previously demonstrated that the infarct size and severity of injury is significantly increased in leptin-deficient obese mice (ob/ob). Here we used a more translational model to evaluate the effect of long term diet-induced obesity (DIO) on stroke outcome using a model of transient ischemic stroke and determined whether the extent of ischaemia influenced outcome and susceptibility to post-stroke infection.Materials and methods. Male C57BL/6 mice were maintained on either a high-fat (60%-fat) or control (12%-fat) diet for 3 and 6 months. Blood pressure, heart rate, blood glucose and bodyweight were monitored throughout the study. Experimental stroke was induced by transient occlusion of the middle cerebral artery (MCAo) by the intraluminal filament method. Mice were culled at 24h after MCAo and brains processed for assessment of ischaemic damage. Lungs were cultured on agar plates and numbers of bacterial colonies were counted at 24h. Histological analysis of lungs was also performed and cytokine and chemokine levels were measured in lung homogenate.Results: A significant increase in ischaemic damage was observed in obese mice after 6 months of high-fat feeding and with a 30min (but not 20min) occlusion of the MCA. There was no difference in the extent of ischaemic damage in mice fed a high-fat diet for 3 months compared to control diet (with a 30min occlusion). At 24h after MCAo, obese mice (6-month) had a greater burden of bacteria in their lungs and histological sings of lung infection. In response to stroke an increase in several cytokines and chemokines were observed in the lungs of control mice at 24h but there was a blunted or altered inflammatory response in the lungs of obese mice.Conclusion: Long-term DIO significantly increases the severity of ischaemic damage in mice after stroke. This detrimental effect of DIO on stroke outcome was dependent on both the severity of obesity and length of ischaemic challenge. Obesity also led to an increased susceptibility to post-stroke lung infection, an observation that might be due to an altered inflammatory response in obese mice.